Effective antigen cross-presentation by prostate cancer patients' dendritic cells: Implications for prostate cancer immunotherapy Journal Article
| Authors: | Orange, D. E.; Jegathesan, M.; Blachère, N. E.; Frank, M. O.; Scher, H. I.; Albert, M. L.; Darnell, R. B. |
| Article Title: | Effective antigen cross-presentation by prostate cancer patients' dendritic cells: Implications for prostate cancer immunotherapy |
| Abstract: | Despite the potency with which dendritic cells (DCs) are able to utilize the exogenous MHC I antigen cross-presentation pathway to cross-present antigen for the activation of killer T cells in model systems, concern about defects in immune function in cancer patients has led to uncertainty regarding whether immune cells derived from patients can effectively be used to generate tumor vaccines. We have undertaken a careful analysis of the potency of using DCs obtained from prostate cancer patients to cross-present antigen derived from human prostate tumor cells for the activation of antigen-specific T cells. Such DCs can be matured ex vivo into functionally active cells and are capable of cross-presenting influenza antigen derived from internalized apoptotic prostate tumor cells. Importantly, we demonstrate effective stimulation of both CD4+ and CD8+ T cells, as evident by production of IFN-γ, and the ability of CD8+ T cells to differentiate into effector CTLs. These results, defining conditions in which prostate cancer patient DCs can efficiently utilize the cross-presentation pathway and in which apoptotic tumor can serve as a source of antigen for DCs to activate T cells, demonstrate that this system warrants clinical study as a potential immunotherapy. © 2004 Nature Publishing Group All rights reserved. |
| Keywords: | controlled study; human cell; drug efficacy; nonhuman; cancer patient; cd8 antigen; cd8-positive t-lymphocytes; animal cell; apoptosis; cell maturation; dendritic cell; tumor cells, cultured; prostate cancer; prostatic neoplasms; lymphocyte differentiation; antigen presentation; dendritic cells; immunotherapy; antigens, neoplasm; gamma interferon; antigen specificity; cd4-positive t-lymphocytes; cytotoxic t lymphocyte; tumor cell; cytokine production; effector cell; cd4 antigen; tumor vaccine; t lymphocyte activation; immunocompetent cell; major histocompatibility antigen class 1; cross-priming; cross-presentation; killer cell; humans; human; male; priority journal; article |
| Journal Title: | Prostate Cancer and Prostatic Diseases |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 1365-7852 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2004-01-01 |
| Start Page: | 63 |
| End Page: | 72 |
| Language: | English |
| DOI: | 10.1038/sj.pcan.4500694 |
| PROVIDER: | scopus |
| PUBMED: | 14999241 |
| DOI/URL: | |
| Notes: | Prostate Cancer Prostatic Dis. -- Cited By (since 1996):7 -- Export Date: 16 June 2014 -- CODEN: PCPDF -- Source: Scopus |
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